Clonidine And Guanfacine

●  Brand Name: Catapress (clonidine), Tenex and Intuniv (Guanfacine)

●  Indications: Clonidine and guanfacine also are used as treatments for attention deficit disorder. They can help reduce anxiety, reduce withdrawal symptoms in those who are on narcotic medications, reduce sweating, and improve sleep when taken at night. There is evidence that they can improve stomach emptying in patients with delayed gastric motility. We have found that a subset of patients with ME/CFS can benefit from the drug, although a randomized trial in adolescents with ME/CFS did not confirm a benefit from clonidine for the group as a whole.

●  Mechanism of Action: Clonidine and Guanfacine are selective alpha-2 adrenergic receptor agonists (sympatholytics), originally developed as antihypertensive drugs to decrease sympathetic nervous system activity in the brain. In individuals with orthostatic intolerance, these medications may cause vasoconstriction, slow the heart rate through a vagal effect, and in some cases, lead to an increase in blood volume.

●  Side Effects: Include increased fatigue, lightheadedness (due to the antihypertensive effect), and dry mouth. If these side effects are mild during the first week, we generally recommend that patients continue the medication to see if the effects resolve and the therapeutic benefits become more apparent over the next few weeks. However, if the side effects are more pronounced, we suggest discontinuing the drug. For patients who have been on clonidine or guanfacine for an extended period, it's important to taper the dose gradually to prevent rebound hypertension. In some cases, patients who initially benefited from clonidine for several months may later experience more severe side effects, such as hot flashes, low blood pressure, and increased fatigue. In these situations, it is often advisable to consider tapering off clonidine slowly to determine if it is contributing to these new issues.

●  Dosage:

  • Clonidine: the usual starting dose for older adolescents and adults is half a tablet (0.05 mg) taken at night for the first seven days, followed by an increase to a full 0.1 mg tablet at night. Higher doses may be well tolerated in some cases. An extended-release formulation is also available.

  • Guanfacine: The starting dose for adolescents and adults is 1 mg per day, with weekly increases of 1 mg, up to a typical maximum dose of 4 mg per day. Higher doses may lead to excessive blood pressure reduction, and in most cases, a daily dose of 1–2 mg is considered optimal.

● Reproductive and Pregnancy Considerations: One report suggests that clonidine use during pregnancy may lead to a slower heart rate in the pregnant individual, which could contribute to lower birth weight in the baby. In cases where clonidine was used to treat high blood pressure, the blood pressure issues themselves may have also played a role in the baby's reduced weight. Clonidine use during pregnancy can cause temporary symptoms in newborns shortly after birth, often referred to as withdrawal. These symptoms may include high or low blood pressure, drowsiness, and irritability. Both clonidine and guanfacine can affect prolactin levels and may reduce milk supply, especially before lactation is well established.

Citations

Arndts, D., & Arndts, K. (1984). Pharmacokinetics and pharmacodynamics of transdermally administered clonidine. European Journal of Clinical Pharmacology, 26(1), 79–85. https://doi.org/10.1007/BF00546713

Bunjes, R., Schaefer, C., & Holzinger, D. (1993). Clonidine and breast-feeding. Clinical Pharmacy, 12(3), 178–179.

Clonidine Hydrochloride [prescribing information]. (2020). East Brunswick, NJ: Unichem Pharmaceuticals (USA) Inc; August.

Gaffney, F. A., Lane, L. B., Pettinger, W., & Blomqvist, C. G. (1983). Effects of long-term clonidine administration on the hemodynamic and neuroendocrine postural responses of patients with dysautonomia. Chest, 83(2 Suppl), 436–438.https://doi.org/10.1378/chest.83.2_supplement.436

Guanfacine Hydrochloride [prescribing information]. (2021). Bridgewater, NJ: Amneal Pharmaceuticals LLC; August.

Intuniv (guanfacine) [prescribing information]. (2020). Lexington, MA: Takeda Pharmaceuticals America, Inc; August.

Miller, A. J., & Raj, S. R. (2018). Pharmacotherapy for postural tachycardia syndrome. Autonomic Neuroscience, 215, 28-36. https://doi.org/10.1016/j.autneu.2018.04.008

Okamoto, L. E., Urechie, V., Rigo, S., Abner, J. J., Giesecke, M., Muldowney, J. A. S., Furlan, R., Shibao, C. A., Shirey-Rice, J. K., Pulley, J. M., Diedrich, A., & Biaggioni, I. (2024). Hyperadrenergic Postural Tachycardia Syndrome: Clinical Biomarkers and Response to Guanfacine. Hypertension (Dallas, Tex. : 1979), 81(11), 2237–2247.https://doi.org/10.1161/HYPERTENSIONAHA.124.23035

Raj S. R. (2013). Postural tachycardia syndrome (POTS). Circulation, 127(23), 2336–2342.https://doi.org/10.1161/CIRCULATIONAHA.112.144501

Watson Laboratories, Inc. (2003). Guanfacine hydrochloride tablets prescribing information. Corona, CA; April.